Dipeptidyl Peptidase-4 Inhibitor Treatment Research Articles

Impact of dipeptidyl peptidase-4 inhibitors on serum adiponectin: a meta-analysis

BackgroundAdiponectin, an adipose-specific protein, is negatively correlated with pro-atherogenic low-density lipoprotein cholesterol (LDL-C) and other cardiovascular risk factors such as insulin resistance. Therefore, low levels of adiponectin are associated with a higher risk for diabetes and cardiovascular disease. Dipeptidyl peptidase-4 inhibitors (DPP4i) have been used for the treatment of type 2 diabetes mellitus (T2DM) as reversible inhibitors through interacting with DPP4 substrate and increase serum incretins such as glucagon-like peptide-1 (GLP-1). The present study aimed to evaluate the effect of DPP4i on serum adiponectin in T2DM patients.MethodsThe PubMed, Embase, and Cochrane library databases were searched from inception to February 2016. Randomized controlled trials, evaluating the DPP4i (sitagliptin and vildagliptin) versus comparator (placebo or active-comparison), in T2DM patients with duration of ≥ 12 weeks, were identified. Weighted differences in means of adiponectin levels were calculated by using a fixed or random-effects model.ResultsTen randomized controlled trials, including 1,495 subjects, were identified. Compared with placebo, DPP4i (sitagliptin and vildagliptin) treatment significantly elevated adiponectin levels by 0.74 μg/mL (95% confidence interval [CI], 0.45 to 1.03) relative to that using an active-comparison by 0.00 μg/mL (95% CI, −0.57 to 0.56). Compared with active-comparison, vildagliptin treatment increased adiponectin levels by 0.32 μg/mL (95% CI, −0.01 to 0.65), whereas sitagliptin treatment decreased adiponectin levels by −0.24 μg/mL (95% CI, −1.07 to 0.58). Trials examining effects of other DPP4i were not found.ConclusionsSitagliptin and vildagliptin increased serum adiponectin levels and had no stronger effect than traditional oral antidiabetic drugs. Further trials with larger sample size are needed to confirm the results and investigate the association between serum adiponectin levels and treatment of other DPP-4 inhibitors.Trial registrationRegistration No in PROSPERO: CRD42016037399.

DPP-4 inhibitors treatment in Chinese type 2 diabetes patients: A meta-analysis

DPP-4 inhibitors treatment in Chinese type 2 diabetes patients: A meta-analysis

Cardiovascular safety of glucose-lowering agents as add-on medication to metformin treatment in type 2 diabetes: report from the Swedish National Diabetes Register.

To investigate the relative safety of various glucose-lowering agents as add-on medication to metformin in type 2 diabetes in an observational study linking five national health registers. Patients with type 2 diabetes who had been on metformin monotherapy and started another agent in addition to metformin were eligible for inclusion. The study period was 2005-2012. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality, cardiovascular disease (CVD), coronary heart disease (CHD), stroke and congestive heart failure (CHF) were estimated using Cox proportional hazards models, weighted for a propensity score. Of the 20 422 patients included in the study, 43% started on second-line treatment with sulphonylurea (SU), 21% basal insulin, 12% thiazolidinedione (TZD), 11% meglitinide, 10% dipeptidyl peptidase-4 (DPP-4) inhibitor, 1% glucagon-like peptide-1 (GLP-1) receptor agonist and 1% acarbose. At the index date, the mean patient age was ~60 years for all groups except the GLP-1 receptor agonist (56.0 years) and SU (62.9 years) groups. Diabetes duration and glycated haemoglobin levels were similar in all groups. When compared with SU, basal insulin was associated with an 18% higher risk and TZD with a 24% lower risk of mortality [HR 1.18 (95% CI 1.03-1.36) and 0.76 (95% CI 0.62-0.94)], respectively. DPP-4 inhibitor treatment was associated with significantly lower risks of CVD, fatal CVD, CHD, fatal CHD and CHF. This nationwide observational study showed that second-line treatment with TZD and DPP-4 inhibitor as add-on medication to metformin were associated with significantly lower risks of mortality and cardiovascular events compared with SU, whereas basal insulin was associated with a higher risk of mortality.

Comparison of charges and resource use associated with saxagliptin and sitagliptin.

ObjectivesSaxagliptin and sitagliptin are two commonly used dipeptidyl peptidase-4 (DPP-4) inhibitors. Little is known about their comparative effectiveness in the real world, particularly their impact on cost and resources use. The objective of this study was to analyze charges and resource use associated with saxagliptin and sitagliptin to understand the impact of these DPP-4 inhibitor treatment options in a real-world setting.MethodsThis was a retrospective, new-user study approved by the Institutional Review Board at the University of Toledo. Data were collected from a US insurance claims dataset (OptumInsight) for patients newly initiating treatment with saxagliptin or sitagliptin between January 1, 2010 and December 31, 2011. ICD-9 code 250 was used to identify patients with T2D. Overall and diabetes-related medical and pharmacy charges were observed. Inpatient hospitalizations were also compared. Propensity score matching was used to balance the cohorts of patients prescribed saxagliptin and sitagliptin. Appropriate univariate statistical tests were applied to the propensity-matched sample to examine differences in resource utilization outcomes. Statistical significance was evaluated at P < 0.05.ResultAfter the propensity score matching, each cohort included 7711 patients. Saxagliptin treatment was associated with lower overall charges ($13,292 vs $14,032; P = 0.0023) and overall medical charges ($9,540 vs $10,296; P = 0.0024) during the 6-month follow-up period compared with sitagliptin treatment. No significant differences were observed in the overall pharmacy charges ($3,751 vs $3,753; P = 0.6937) and the diabetes-related charges ($5,141 vs $5,232; P = 0.2957). All-cause and diabetes-related inpatient hospitalization rates were significantly lower with saxagliptin treatment (p = 0.0001 and p = 0.0019, respectively). All-caused inpatient charges were also significantly lower with saxagliptin ($2,917.26 vs $3445.89; P < 0.0001).ConclusionCompared with patients initiating sitagliptin treatment, patients initiating saxagliptin treatment reported lower overall and medical charges and lower overall and diabetes-related hospitalization rates. These findings may aid payers in managing patients with T2D.

The dipeptidyl peptidase-4 inhibitor may improve the insulin secretion in type 2 diabetes patients just after starting hemodialysis treatment: preliminary study

Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become widely used in hemodialysis patients with type 2 diabetes mellitus (T2DM). This study aimed at testing the hypothesis that administration of alogliptin, a DPP-4i, soon after hemodialysis initiation improves beta cell function in hemodialysis patients with T2DM. Patients with end-stage renal disease and T2DM (n = 10) not previously treated with DPP-4i (mean age, 54.2 years) were enrolled. The study end point was the acute insulin response to glucose assessed by a frequently sampled intravenous glucose tolerance test (IVGTT) that was conducted during the hemodialysis session just before lunch using an external circulation circuit. All patients received 6.25 mg alogliptin for 2 weeks. Blood glucose (Glu), serum insulin (IRI), and C-peptide (CPR) were measured before (0 min) in addition to 5 and 15 min after the glucose load. Glucagon-like peptide-1 (GLP-1) was measured before the glucose load. Glu(0) significantly decreased after the 2-week DPP-4i treatment (174 ± 20 vs. 150 ± 27 mg/dL, P = 0.023). IRI(5) significantly increased after the DPP-4i treatment (14.6 ± 31.7 vs. 23.4 ± 16.6 μU/mL, P = 0.038), but IRI(0) and IRI(15) did not change significantly. GLP-1 also significantly increased after the DPP-4i treatment (6.6 ± 4.4 vs. 2.6 ± 0.8 pmol/L, P = 0.012). Inhibition of DPP-4 with alogliptin improved endogenous insulin secretion in response to intravenous glucose in hemodialysis patients with T2DM.

Clinical and genetic predictors of dipeptidyl peptidase-4 inhibitor treatment response in Type 2 diabetes mellitus.

To determine the clinical and genetic predictors of the dipeptidyl peptidase-4 (DPP-4) inhibitor treatment response in Type 2 diabetes mellitus (T2DM) patients. DPP4, WFS1 and KCNJ11 gene polymorphisms were genotyped in a cohort study of 662 T2DM patients treated with DPP-4 inhibitors sitagliptin, vildagliptin or linagliptin. Genotyping was performed by Applied Biosystems TaqMan SNP genotyping assay. Patients with triglyceride levels less than 1.7 mmol/l (odds ratio [OR]: 2.2.; 95% CI: 1.031-4.723), diastolic blood pressure (DBP) less than 90 mmHg (OR: 1.7; 95% CI: 1.009-2.892) and KCNJ11 rs2285676 (genotype CC) (OR: 2.0; 95% CI: 1.025-3.767) were more likely to response to DPP-4 inhibitor treatment compared with other patients, as measured by HbA1c levels. Triglycerides, DBP and KCNJ11 rs2285676 are predictors of the DPP-4 inhibitor treatment response in T2DM patients.

Discovery of gastric inhibitory polypeptide and its subsequent fate: Personal reflections

The present review focuses initially on experimental studies that were designed to identify acid inhibitory factors, referred to as ‘enterogastrones,’ that ultimately led to the isolation of gastric inhibitory polypeptide (GIP), a 42‐amino acid polypeptide. GIP was shown to inhibit acid secretion in animal models, as well as stimulating gastric somatostatin secretion. However, its role in human gastric physiology is unclear. Further studies showed that GIP strongly stimulated the secretion of insulin, in the presence of elevated glucose, and this ‘incretin’ action is now considered to be its most important; an alternative for the GIP acronym, glucose‐dependent insulinotropic polypeptide, was therefore introduced. In the 1970s, GIP purified by conventional chromatography was shown by high‐performance liquid chromatography to consist largely of GIP 1‐42 and GIP 3‐42. It was later shown that dipeptidyl peptidase 4 was a physiologically relevant enzyme responsible for this conversion, as well as the similar metabolism of the second incretin, glucagon‐like peptide‐1. Dipeptidyl peptidase‐4 inhibitors are currently in use as type 2 diabetes therapeutics, and studies on islet transplantation in rodent models of type 1 diabetes have shown that dipeptidyl peptidase‐4 inhibitor treatment reduces graft rejection. Additional studies on C‐terminally shortened forms of GIP have shown that GIP 1‐30 and a dipeptidyl peptidase‐4‐resistant form (D‐Ala2 GIP 1‐30) are equipotent to the intact polypeptide in vitro, and administration of D‐Ala2 GIP 1‐30 to diabetic rodents greatly improved glucose tolerance and reduced apoptotic cell death in islet β‐cells. There are probably therefore further clinically useful effects of GIP that require investigation.

Reduced DPP4 activity improves insulin signaling in primary human adipocytes

DPP4 is a ubiquitously expressed cell surface protease which is also released to the circulation as soluble DPP4 (sDPP4). Recently, we identified DPP4 as a novel adipokine oversecreted in obesity and thus potentially linking obesity to the metabolic syndrome. Furthermore, sDPP4 impairs insulin signaling in an autocrine and paracrine fashion in different cell types. However, it is still unknown which functional role DPP4 might play in adipocytes. Therefore, primary human adipocytes were treated with a specific DPP4 siRNA. Adipocyte differentiation was not affected by DPP4 silencing. Interestingly, DPP4 reduction improved insulin responsiveness of adipocytes at the level of insulin receptor, proteinkinase B (Akt) and Akt substrate of 160 kDa. To investigate whether the observed effects could be attributed to the enzymatic activity of DPP4, human adipocytes were treated with the DPP4 inhibitors sitagliptin and saxagliptin. Our data show that insulin-stimulated activation of Akt is augmented by DPP4 inhibitor treatment. Based on our previous observation that sDPP4 induces insulin resistance in adipocytes, and that adipose DPP4 levels are higher in obese insulin-resistant patients, we now suggest that the abundance of DPP4 might be a regulator of adipocyte insulin signaling.

Incretin-based therapy: renal effects

Glucagon like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors are new classes of hypoglycemic agents with numerous pleiotropic effects. The review summarises data about the influence of GLP-1 analogues and DPP-4 inhibitors on structural and functional changes in diabetic kidneys. Growing evidence indicates that the kidney is one of the loci of the effects and degradation of GLP-1. The potency of the effects of GLP-1 in diabetic kidneys can be reduced by decrease in GLP-1 receptor expression or enhancement of GLP-1 degradation. In experimental models of diabetic nephropathy and non-diabetic renal injury, GLP-1 analogues and DPP-4 inhibitors slow the development of kidney fibrosis and prevent the decline of kidney function. The mechanisms of protective effect include hyperglycaemia reduction, enhancement of sodium excretion, suppression of inflammatory and fibrogenic signalling pathways, reduction of oxidative stress and apoptosis in the kidneys. In clinical studies, the urinary albumin excretion reduction rate while using the GLP-1 analogue and DPP-4 inhibitor treatment was demonstrated in patients with type 2 diabetes. Long-term impact of these agents on renal function in diabetes needs further investigations.

The Difficulty of Diabetic Therapy: An Observational Retrospective Study from Actual Clinical Practice

Aim: The main purpose for a good management of the diabetic disease is to avoid blood glucose swings. This study aims to analyze the diabetic management focusing on iatrogenic hypoglycemia, the therapeutic failure and the Body Mass Index (BMI). Methods: Diabetic patients were divided into insulin/secretagogue drugs (insulin/SD), Glucagon Like Peptide-1 Receptor Agonist (GLP-1RA) and Dipeptidylpeptidase-4 inhibitors (DPP-4i). An algorithm was created to identify hypoglycemic events, considering fracture discharge, access to emergency for coma or driving mishaps, and Self- Monitoring Blood Glucose. The achievement of glycated hemoglobin (HbA1c) target level (≤ 7%) and BMI target (≤ 25 kg/m2) were analyzed as well. Results: 16.23% out of 16,549 patients had at least one hypoglycemic event. Patients taking insulin/SD (94.39%) had a major risk of hypoglycemia (OR=2.01 p<0.001), while the groups with GLP-1 RA (1.87%) and DPP-4i (3.47%) show an OR of 0.59 (p<0.001) and 0.44 (p<0.001), respectively. The therapeutic target of HbA1c was achieved only in patients treated with DPP-4i (6.85% p<0.001). The BMI remained over the target threshold both before and during treatment for all groups but increased only for patients with insulin/SD (from 29.29 to 29.58 kg/m2). The major decrease in the number of BMI off-target patients was reported for the DPP-4i group (86.2% and 80.1% before and during treatment). Conclusions: The DPP-4i treatment did not associate with hypoglycemia and allowed HbA1c target achievement. Insulin/SD therapy, in contrast, correlated with an increased risk of hypoglycemic events, weight gain, and failure to achieve hematic target with HbA1c.

Lessons learned from cardiovascular outcome clinical trials with dipeptidyl peptidase 4 (DPP-4) inhibitors.

Previous trials of glucose-lowering strategies in subjects with type 2 diabetes have demonstrated a beneficial effect of intensive glycemic control on microvascular complications but failed to show a clear benefit on cardiovascular complications. The findings of meta-analyses of rosiglitazone trials suggesting that rosiglitazone might increase the risk of myocardial infarction have cast doubt on the cardiovascular safety of glucose-lowering drugs. In 2008, the US Food and Drug Administration has implemented rigorous criteria to approve new glucose-lowering drugs, requiring proof of cardiovascular safety. These regulatory requirements have led to a considerable increase in the number of cardiovascular outcome trials in type 2 diabetes to ensure that newer glucose-lowering drugs are not associated with increased cardiovascular risk. Incretin-based therapies including dipeptidyl peptidase 4 (DPP-4) inhibitors, and injectable glucagon-like peptide 1 (GLP-1) receptor agonists are novel treatment options for patients with inadequate glucose control. Although DPP-4 inhibitors have shown neutral effects on risk factors for cardiovascular diseases, it remains unclear whether treatment with these new glucose-lowering agents might be associated with a reduction in cardiovascular events. The results of the three cardiovascular outcome trials comparing DPP-4 inhibitors treatment to placebo in addition to other glucose-lowering drugs have been published. All the three DPP-4 inhibitor cardiovascular outcome trials have shown non-inferiority with regard to cardiovascular safety, compared with placebo, when added to usual care. In this review, we summarize cardiovascular outcome trials of DPP-4 inhibitors, and provide an overview of these trials and their limitations.

Short‐term and long‐term effects of dipeptidyl peptidase‐4 inhibitors in type 2 diabetes mellitus patients with renal impairment: a meta‐analysis of randomized controlled trials

To assess the short-term and long-term effects of dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes mellitus patients with renal impairment, a meta-analysis of randomized clinical trials of DPP-4 inhibitor interventions in type 2 diabetes mellitus patients with renal impairment was performed. PubMed, Embase, Cochrane Library and ClinicalTrials.gov were searched through the end of March 2015. Randomized clinical trials were selected if (1) DPP-4 inhibitors were compared with a placebo or other active-comparators, (2) the treatment duration was ≥12weeks and (3) data regarding changes in haemoglobin A1c (HbA1c ), changes in fasting plasma glucose or hypoglycaemia and other adverse events were reported. Of 790 studies, ten studies on eight randomized clinical trials were included. Compared with the control group, DPP-4 inhibitors were associated with a greater HbA1c reduction in both the short-term [mean differences (MD) = -0.45, 95% confidence intervals (-0.57, -0.33), p < 0.0001] and long-term [MD = -0.33, 95% confidence intervals (-0.63, -0.03), p = 0.03] treatments. However, the long-term greater reduction in HbA1c with DPP-4 inhibitor treatment was only significant when the control treatment comprised placebo plus stable background treatment, but not glipizide plus stable background treatment. DPP-4 inhibitors were associated with a greater fasting plasma glucose reduction [MD = -12.59, 95% confidence intervals (-22.01, -3.17), p = 0.009] over the short-term; however, this effect was not present over the long-term. Regarding the hypoglycaemia adverse events assessment, the long-term treatment data indicated there was no increased risk of hypoglycaemia compared with placebo or active-controlled anti-diabetic drugs. The present meta-analysis confirms that DPP-4 inhibitors are effective and equivalent to other agents in type 2 diabetes mellitus patients with renal impairment. Copyright © 2015 John Wiley & Sons, Ltd.

DPP‐4 inhibitors and risk of infections: a meta‐analysis of randomized controlled trials

To evaluate the risk of infections in the treatment of type 2 diabetes patients with dipeptidyl-peptidase 4 (DPP-4) inhibitors. A literature search was conducted through electronic databases. The inclusion criteria included study duration of no less than 12 weeks developed in type 2 diabetes patients, the use of a randomized control group receiving a DPP-4 inhibitor and the availability of outcome data for infections. Out of 2181 studies, 74 studies were finally included. The risk of overall infection for DPP-4 inhibitors treatment was comparable to placebo (odds ratio (OR) = 0.97, 95% confidence interval (CI), 0.91 to 1.04, p = 0.40), metformin treatment (OR = 1.22, 95% CI, 0.95 to 1.56, p = 0.12), sulphonylurea treatment (OR = 1.09, 0.93 to 1.29, p = 0.29), thiazolidinedione treatment (OR = 0.86, 95% CI, 0.65 to 1.14, p = 0.29) and alpha glucosidase inhibitor treatment (OR = 1.03, 95% CI, 0.33 to 3.22, p = 0.96). When compared different DPP-4 inhibitors with placebo treatment, risks of infections were comparable for alogliptin, linagliptin, sitagliptin, saxagliptin and vildagliptin. Compared with placebo or active comparator treatment, risks of infection in different systems for DPP-4 inhibitors were all comparable. The overall risk of infections of DPP-4 inhibitor was not increased compared with control groups.

Autonomic Diabetic Neuropathy Impairs Glucose and Dipeptidyl Peptidase 4 Inhibitor-Regulated Glucagon Concentration in Type 1 Diabetic Patients

Background: Dipeptidyl peptidase 4 inhibitors (DPP4i) could exert their glucagonostatic action through a functional autonomic nervous system independently from insulin secretion. We explored this hypothesis. Methods: We studied C-peptide negative type 1 diabetic patients (T1D) with (AN+) or without (AN-) autonomic neuropathy. Plasma glucagon, active and total glucagon-like peptide-1 (GLP-1), GIP, pancreatic polypeptide (PP), and glucose concentrations were quantified over 180 minutes following a meal test. Furthermore, to increase the plasma concentration of GLP-1 between groups and study its impact on glucagon secretion, 50 mg of vildagliptin and a second meal test were administered to the same patients. Results: The plasma concentration of glucagon was higher in AN+ patients than in AN- patients, which was associated with lower PP and active GLP-1 plasma concentrations. This first set of data suggest that AN, presumably involving parasympathetic activity, results in loss of glucose-regulated glucagon secretion. After DPP4i treatment, AN+ patients lost the ability to suppress plasma glucagon, and the low plasma PP responses were not restored. Conclusions: We here show that a functional autonomic nervous system is required for the proper control of glucagon secretion. The mechanism is insulin-independent. The glucagonostatic action of DPP4i also requires this mechanism. J Endocrinol Metab. 2015;5(4):229-237 doi: http://dx.doi.org/10.14740/jem289w

Renoprotective effects of incretin-based drugs: A novel pleiotropic effect of dipeptidyl peptidase-4 inhibitor.

Renoprotective effects of incretin-based drugs: A novel pleiotropic effect of dipeptidyl peptidase-4 inhibitor.

Dipeptidyl peptidase-4 inhibition ameliorates Western diet-induced hepatic steatosis and insulin resistance through hepatic lipid remodeling and modulation of hepatic mitochondrial function.

Novel therapies are needed for treating the increasing prevalence of hepatic steatosis in Western populations. In this regard, dipeptidyl peptidase-4 (DPP-4) inhibitors have recently been reported to attenuate the development of hepatic steatosis, but the potential mechanisms remain poorly defined. In the current study, 4-week-old C57Bl/6 mice were fed a high-fat/high-fructose Western diet (WD) or a WD containing the DPP-4 inhibitor, MK0626, for 16 weeks. The DPP-4 inhibitor prevented WD-induced hepatic steatosis and reduced hepatic insulin resistance by enhancing insulin suppression of hepatic glucose output. WD-induced accumulation of hepatic triacylglycerol (TAG) and diacylglycerol (DAG) content was significantly attenuated with DPP-4 inhibitor treatment. In addition, MK0626 significantly reduced mitochondrial incomplete palmitate oxidation and increased indices of pyruvate dehydrogenase activity, TCA cycle flux, and hepatic TAG secretion. Furthermore, DPP-4 inhibition rescued WD-induced decreases in hepatic PGC-1α and CPT-1 mRNA expression and hepatic Sirt1 protein content. Moreover, plasma uric acid levels in mice fed the WD were decreased after MK0626 treatment. These studies suggest that DPP-4 inhibition ameliorates hepatic steatosis and insulin resistance by suppressing hepatic TAG and DAG accumulation through enhanced mitochondrial carbohydrate utilization and hepatic TAG secretion/export with a concomitant reduction of uric acid production.

Effects of Sitagliptin on Insulin and Glucagon Levels in Type 2 Diabetes Mellitus.

Effects of Sitagliptin on Insulin and Glucagon Levels in Type 2 Diabetes Mellitus.

Letter: economic impact of combining metformin with dipeptidyl peptidase-4 inhibitors in diabetic patients with renal impairment in spanish patients (diabetes metab j 2015;39:74-81).

Dipeptidyl peptidase-4 (DPP4) inhibitor is one of the most commonly prescribed diabetic medications in recent times. The strong points of DPP4 inhibitor are low risk of hypoglycemia and weight gain [1,2]. However, the relatively expensive cost of DPP4 inhibitor compared with pre-existing medications is an obstacle for the use of DPP4 inhibitor in clinical practice. In this article entitled Economic impact of combining metformin with dipeptidyl peptidase-4 inhibitors in diabetic patients with renal impairment in Spanish Sicras-Mainar and Navarro-Artieda [3] compared the total cost of DPP4 inhibitor and other oral anti-diabetics including sulfonylureas, glinides, and thiazolidinediones (TZDs) over 2 years of follow-up. The authors reported that the total economic cost of DPP4 inhibitor treatment could be lower than other oral antidiabetic (OAD) treatment for type 2 diabetic patients with renal impairment. In this study, DPP-4 inhibitors showed better compliance, better metabolic control, and lower hypoglycemia than other OAD. It is interesting that DPP4 inhibitor was cost-effective and safe even for relatively old (mean age 70.2±10.4), renal impaired (chronic kidney disease stage 1 to 3) patients. However, this study has some points that should be discussed. Previous studies reported that DPP4 inhibitor showed beneficial effects on cardiovascular events [4,5]. In this study, lower hospital care costs of DPP4 inhibitor group was observed with lower hypoglycemic events. DPP4 inhibitor group also showed lower primary care costs, including drug cost. Considering that the drug costs of DPP4 inhibitors are relatively high, especially compared with sulfonylurea, the reason for the lower drug cost of DPP4 inhibitor group compared with other OAD group may need further explanation. Separate analysis of insulin secretagogues and TZDs in other OAD group could be helpful. In this study, metabolic control rate, defined by the ratio of glycosylated hemoglobin (HbA1c) lower than 7.0%, was used for glycemic control, and it was better in DPP4 inhibitor group than other OAD group after 24 months of follow-up, even though baseline metabolic rates were not different. Sulfonylurea and TZD have been known to show better glucose-lowering effect than DPP4 inhibitor, and poor glycemic control subjects are more likely to take sulfonylurea or TZD. Therefore, using baseline HbA1c level could be more appropriate to compare the overall glucose lowering effect of each group. As a result, this study showed that a DPP4 inhibitor could be an attractive choice for treatment of old-aged, renal impairment diabetic patients, with even lower total economic costs. Further studies to assess the economic points in diabetic treatments should be conducted to figure out the sharply increasing economic costs in type 2 diabetes.

Predictive Factors for Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus.

BackgroundPredictive factors for the efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors for lowering glycosylated hemoglobin (HbA1c) remain unclear in patients with type 2 diabetes mellitus. The aim of this study is therefore to clarify predictive factors of the efficacy of DPP-4 inhibitors for lowering HbA1c after 12 months of treatment.MethodsA total of 191 consecutive type 2 diabetic patients (male sex 55%, mean age, 68.3±35.8 years), who had been treated with DPP-4 inhibitors for 12 months, were enrolled in this study and evaluated retrospectively.ResultsAfter 12 months of DPP-4 inhibitor treatment, random blood glucose level, and HbA1c level, decreased from 167±63 to 151±49 mg/dL (P<0.01), and from 7.5%±1.3% to 6.9%±0.9% (P<0.01) respectively, without severe side effects. Multiple regression analysis showed that predictors of DPP-4 inhibitor treatment efficacy in lowering HbA1c level after 12 months were a decrease in HbA1c level after 3 months of treatment, a high baseline HbA1c level, a low baseline body mass index, and the absence of coronary artery disease.ConclusionMost suitable candidates for treatment with DPP-4 inhibitors are diabetics who are not obese and do not have coronary artery disease. In addition, long-term efficacy of DPP-4 inhibitors can be predicted by decrement of HbA1c after 3 months of treatment.

The association of WFS1 gene polymorphisms with the DPP-4 inhibitors treatment response in type 2 diabetes

The association of WFS1 gene polymorphisms with the DPP-4 inhibitors treatment response in type 2 diabetes